Chemotherapeutic agents



Patented Oct. 18, 1949 CHEMOTHERAPEUTIC AGENTS Gustav J. Martin, Philadelphia, Pa., assignor to The National Drug Company, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Application October 15, 1946, Serial No. 703,281

1 Claim. 1

This invention relates to improved chemotherapeutic agents and more particularly refers to compounds of the sulfonamide group whose activity is markedly increased by employing them in admixture with tryptophane displacers.

It is an object of this invention to produce new chemotherapeutic agents having superior therapeutic activity. A further object is to increase the therapeutic activity of sulfonamides whereby substantially smaller amounts thereof may be employed while obtaining the full effectiveness of the customary dosages. Additional objects will become apparent from a consideration of the following description and claim.

In accordance with this invention I have found that when a member of the well-known class of tryptophane displacers is mixed with a member of the sulfonamide group, the resulting composition is synergistic in that it possesses a chemotherapeutic activity which is substantially greater than the sum total of the activity of the two ingredients. For example, 1 M. E. C. (min imum effective concentration) of sulfathiazole has by definition the same antibacterial power as 1 M. E. C. of 5-methyl-tryptophane. By mixing 0.1 M. E. C. of sulfathiazole with 0.1 M. E. C. of B-methyl-tryptophane I have found that the same antibacterial action is obtained as though 1 M. E. C. of either agent had been employed. This means that the same chemotherapeutic effect could be obtained using 0.1 the dosage of either compound. Since the toxicity of the sulfonamides is generally recognized and presents a serious problem in their use, this invention permits the desirable results of these compounds to be obtained while markedly minimizing their undesirable efiects. My compositions evidence improved effectiveness for either internal or external use.

A further example of the effectiveness of these compositions comprises the treatment of pneumococcic pneumonia in adults. For the treatment of this condition sulfathiazole is frequently used in an initial dose of 4 grams, followed by 1 gram each 4 hours day and night until the patients temperature has been normal for 72 hours. This is a substantial intake of sulfathiazole and frequently produces undesirable toxic effects. By employing a mixture containing equal amounts of sulfathiazole and S-methyltryptophane, the foregoing dosage could be reduced to an initial 0.8 gram of the combination plus 0.2 gram each 4 hours without any noticeable sacrifice in the beneficial effects thereof. As a result, the expected undesirable effects of the sulfathiazol can be entirely avoided or substantially minimized. Needless to say this is of tremendous advantage to the patient.

The sulionamides which may be employed herein are well known and include sulfathiazole,

2 sulfadiazine, sulfanilamide, sulfapyridine, and the like. It is also contemplated that other chemotherapeutic agents, particularly those having a bacteriostatic action, may be employed in the compositions of this invention either in place of or in admixture with the sulfonamides. Likewise it is contemplated that one or more sulfonamides may be incorporated in these compositions, although as a general rule one of these agents is suflicient.

Tryptophane displacers are a well-known group of chemical compounds which have the effect of displacing the amino acid tryptophane when administered. They are represented by the compounds 5-methyl-tryptophane, styrylacrylic acid, styrylacetic acid, thienylalanine, and the {like Of those displacers I prefer 5-methy1- tryptophane.

The compositions of my invention are made merely by mixing the sulfonamide and the tryptophane displacer. The mixture may be incorporated in capsules, tablets, etc., in accordance with standard practice. For optimum results I prefer to use 1 part by weight of the sulfonamide to an amount of tryptophane displacer within the range of /2 to 2 parts by weight. In other words, the ratio of sulfonamide to displacer may vary from 1 to 2 or 2 to 1 by weight. I have found that amounts of the foregoing agents outside of the preferred range produce desirable results, and it should be understood that the ratio by weight of sulfonamide to displacer may vary from 1 to 10 to 10 to 1, with noticeable improvement on the therapeutic activity of the ingredients.

By means of this invention much smaller amounts of sulfonamides may be employed in order to avoid their toxic effects without sacrificing their desirable therapeutic properties. In the same manner, a standard dose of sulfonamide may be employed to give a therapeutic effect approximately ten times that of this agent alone by combining it with a, tryptophane displacer as aforesaid.

As many apparently widely different embodiments of this invention maybe made without departing from the spirit and scope hereof, it is to be understood that the invention is not limited tothe specific embodiments hereof except as defined in the appended claim.

I claim:

A synergistic composition comprising from 1 to 10 parts by weight of sulfathiazole and from 10 to 1 parts by weight of 5-methyl-tryptophane.

GUSTAV J. MARTIN.

REFERENCES CITED The following references are of record in the file of this patent:

Anderson in Science, June 1, 1945, pages 565 and 566. (Copy in Patent Office Scientific Library.) 

